Tumor proliferation and invasion are intrinsically coupled and unraveled through tunable spheroid and physics-based models.

Autor: Crawford AJ; Department of Chemical and Biomolecular Engineering, Johns Hopkins University, 3400N Charles St, Baltimore, MD 21218, USA; Johns Hopkins Physical Sciences-Oncology Center and Institute for NanoBioTechnology, Johns Hopkins University, 3400N Charles St, Baltimore, Maryland 21218, USA., Gomez-Cruz C; Department of Continuum Mechanics and Structural Analysis, Universidad Carlos III de Madrid, Avda. de la Universidad 30, 28911 Leganes, Madrid, Spain; Departamento de Bioingenieria, Universidad Carlos III de Madrid, Avda. de la Universidad 30, 28911 Leganes, Madrid, Spain., Russo GC; Department of Chemical and Biomolecular Engineering, Johns Hopkins University, 3400N Charles St, Baltimore, MD 21218, USA; Johns Hopkins Physical Sciences-Oncology Center and Institute for NanoBioTechnology, Johns Hopkins University, 3400N Charles St, Baltimore, Maryland 21218, USA., Huang W; Johns Hopkins Physical Sciences-Oncology Center and Institute for NanoBioTechnology, Johns Hopkins University, 3400N Charles St, Baltimore, Maryland 21218, USA; Department of Biology, Johns Hopkins University, 3400N Charles St, Baltimore, Maryland 21218, USA., Bhorkar I; Johns Hopkins Physical Sciences-Oncology Center and Institute for NanoBioTechnology, Johns Hopkins University, 3400N Charles St, Baltimore, Maryland 21218, USA; Department of Biomedical Engineering, Johns Hopkins University, 3400N Charles St, Baltimore, Maryland 21218, USA., Roy T; Department of Chemical and Biomolecular Engineering, Johns Hopkins University, 3400N Charles St, Baltimore, MD 21218, USA; Johns Hopkins Physical Sciences-Oncology Center and Institute for NanoBioTechnology, Johns Hopkins University, 3400N Charles St, Baltimore, Maryland 21218, USA., Muñoz-Barrutia A; Department of Chemical and Biomolecular Engineering, Johns Hopkins University, 3400N Charles St, Baltimore, MD 21218, USA; Departamento de Bioingenieria, Universidad Carlos III de Madrid, Avda. de la Universidad 30, 28911 Leganes, Madrid, Spain; Area de Ingenieria Biomedica, Instituto de Investigacion Sanitaria Gregorio Maranon, Calle del Doctor Esquerdo 46, Madrid' ES 28007, Spain., Wirtz D; Department of Chemical and Biomolecular Engineering, Johns Hopkins University, 3400N Charles St, Baltimore, MD 21218, USA; Johns Hopkins Physical Sciences-Oncology Center and Institute for NanoBioTechnology, Johns Hopkins University, 3400N Charles St, Baltimore, Maryland 21218, USA; Department of Biomedical Engineering, Johns Hopkins University, 3400N Charles St, Baltimore, Maryland 21218, USA; Departments of Pathology and Oncology and Sydney Kimmel Comprehensive Cancer Center, The Johns Hopkins School of Medicine, 1800 Orleans St, Baltimore, MD 21215, USA. Electronic address: wirtz@jhu.edu., Garcia-Gonzalez D; Department of Continuum Mechanics and Structural Analysis, Universidad Carlos III de Madrid, Avda. de la Universidad 30, 28911 Leganes, Madrid, Spain. Electronic address: danigarc@ing.uc3m.es.
Jazyk: angličtina
Zdroj: Acta biomaterialia [Acta Biomater] 2024 Feb; Vol. 175, pp. 170-185. Date of Electronic Publication: 2023 Dec 29.
DOI: 10.1016/j.actbio.2023.12.043
Abstrakt: Proliferation and invasion are two key drivers of tumor growth that are traditionally considered independent multicellular processes. However, these processes are intrinsically coupled through a maximum carrying capacity, i.e., the maximum spatial cell concentration supported by the tumor volume, total cell count, nutrient access, and mechanical properties of the tissue stroma. We explored this coupling of proliferation and invasion through in vitro and in silico methods where we modulated the mechanical properties of the tumor and the surrounding extracellular matrix. E-cadherin expression and stromal collagen concentration were manipulated in a tunable breast cancer spheroid to determine the overall impacts of these tumor variables on net tumor proliferation and continuum invasion. We integrated these results into a mixed-constitutive formulation to computationally delineate the influences of cellular and extracellular adhesion, stiffness, and mechanical properties of the extracellular matrix on net proliferation and continuum invasion. This framework integrates biological in vitro data into concise computational models of invasion and proliferation to provide more detailed physical insights into the coupling of these key tumor processes and tumor growth. STATEMENT OF SIGNIFICANCE: Tumor growth involves expansion into the collagen-rich stroma through intrinsic coupling of proliferation and invasion within the tumor continuum. These processes are regulated by a maximum carrying capacity that is determined by the total cell count, tumor volume, nutrient access, and mechanical properties of the surrounding stroma. The influences of biomechanical parameters (i.e., stiffness, cell elongation, net proliferation rate and cell-ECM friction) on tumor proliferation or invasion cannot be unraveled using experimental methods alone. By pairing a tunable spheroid system with computational modeling, we delineated the interdependencies of each system parameter on tumor proliferation and continuum invasion, and established a concise computational framework for studying tumor mechanobiology.
Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)
Databáze: MEDLINE
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